Axial specification in bilateral organisms is regulated by the expression of homeotic cluster/homeobox-containing (HOM-C/Hox) genes. Changes in HOM-C/Hox expression patterns have been correlated with changes in vertebrate and invertebrate body plans. In humans and other mammals, altered cervical vertebrae specification due to defects in HOM-C/Hox gene expression patterns is associated with thoracic outlet syndrome and early childhood cancer. Despite the overwhelming evidence for the role of HOM-C/Hox genes in axial specification, little is known about the evolutionary mechanisms that lead to altered HOM-C/Hox gene expression patterns and hence to altered body plans. The research proposed in this application will address the evolution of axial specification in the nematode genus Caenorhabditis. In Caenorhabditis, the pattern of sensory rays in the male tail and the size of the vulval equivalence group are determined by positional information imparted from HOM-C/Hox genes. Both of these characters have changed during the evolution of C. briggsae. The overall goal of the research proposed in this application is to determine the genetic basis of these changes. Specific aims are: 1. to determine the number of genes involved in the evolution of these characters; 2. to determine if changes in ray pattern and in the vulval equivalence group have a common genetic basis; and 3. to map and identify those genes responsible for ray pattern and vulva equivalence group evolution. These aims will be achieved through genetic analyses of C. briggsae variant strains that exhibit ancestral phenotypes for ray pattern and for specification of cell fates in the vulval equivalence group. Gene number will be determined from the frequency with which parental strains are recovered following crosses between C. briggsae variants that express ancestral and derived characters. Cosegregation of ray pattern and vulval equivalence group phenotypes will be evidence of a common genetic basis. Genes will be mapped and identified using multifactor data from such crosses.